Synergy between low-dose ranitidine and antacid in decreasing gastric and oesophageal acidity and relieving meal-induced heartburn

BACKGROUND: The pathophysiology of recurrent postprandial heartburn and the basis for the effectiveness of antacids or low doses of histamine H2-receptor antagonists have not been well studied. METHODS: The selected subjects (n=26) had heartburn more than four times a week for at least 2 months, which was responsive to antacids. Gastric pH and oesophageal pH were measured for 1 h before, during, and 4.5 h after ingestion of a meal over 0.5 h. Heartburn severity was assessed at 15-min intervals beginning at the end of the meal. Each subject randomly received placebo, 75 mg ranitidine, 420 mg calcium carbonate, and ranitidine plus calcium carbonate. Values for pH were converted to acid concentration (mM) and integrated acidity was calculated from the cumulative, time-weighted means of the acid concentrations for every second of the postprandial recording period. RESULTS: There was a close temporal relationship between heartburn and oesophageal acidity. Most oesophageal acid exposure occurred over a 90-min period that began approximately 45 min after the end of the meal. During this period the gastric acid concentration was less than 5% of maximal. Ranitidine significantly decreased gastric but not oesophageal acidity, whilst antacid significantly decreased oesophageal but not gastric acidity. Ranitidine plus antacid significantly decreased both gastric and oesophageal acidity. Antacid alone and ranitidine plus antacid significantly decreased heartburn severity. CONCLUSIONS: Determining integrated gastric and oesophageal acidity provides novel information regarding the pathophysiology of meal-induced heartburn as well as the actions of low-dose ranitidine and antacid. For subjects with meal-induced heartburn, treatment with low-dose ranitidine plus antacid is particularly effective in decreasing gastric and oesophageal acidity as well as heartburn severity.     

Clinical effectiveness of a new antacid chewing gum on heartburn and oesophageal pH control

BACKGROUND: Oesophageal acid neutralization with antacids depends on the duration of oesophageal antacid exposure and acid neutralizing capacity. A gum that releases antacid as it is chewed could take advantage of both mechanisms to enhance heartburn relief. METHODS: Twenty-four subjects were crossed over to four regimens: placebo, chewable antacid tablets (1000 mg CaCO3), lower dose gum (600 mg CaCO3) and higher dose gum (900 mg CaCO3). A dual pH probe was placed, subjects ate a standardized provocative meal and self-dosed once as needed. Symptoms were recorded every 15 min using visual analogue and Likert scales. RESULTS: SYMPTOMS: Both gums decreased heartburn compared to placebo for 120 min. Higher dose gum decreased heartburn more than chewable antacids up to 120 min post-dose. pH: Active chewable antacid and gums immediately increased oesophageal pH, with significant improvement 15-30 min post-dose. SUMMARY: (i) both gums promptly decreased heartburn and elevated oesophageal pH; (ii) both gums provided sustained relief for 120 min; (iii) antacid gums provided faster and more prolonged symptom relief and pH control than chewable antacids. CONCLUSIONS: Calcium carbonate gum effectively neutralizes oesophageal acidity and relieves symptoms following a meal, and is superior to chewable antacids in terms of the duration of heartburn relief.     

Continuous distal oesophageal acidification decreases postprandial gastric acidity in healthy human subjects

Background  Previously, we hypothesized that exposing the distal oesophagus to acid signals the stomach to decrease gastric acidity.
Aim  To test the hypothesis that exposing the distal oesophagus to acid signals the stomach to decrease gastric acidity.
Methods  Twenty-two healthy humans ingested a standard meal containing [¹⁴C]octanoic acid and [¹³C]glycine over 30 min on 2 separate occasions. Gastric pH was measured for 90 min before and 240 min after the meal. 10 m m HCl was infused continuously at 1 mL/min into either the distal oesophagus or stomach in a 2-way crossover fashion for 60 min before and 240 min after the meal. Gastric emptying of solid and liquid were determined with breath tests.
Results  Compared to gastric infusion, oesophageal infusion significantly decreased gastric acidity after the meal, but not before the meal and the magnitude of the decrease varied directly with gastric acidity. Gastric emptying of solid or liquid with oesophageal infusion was not significantly different from that with gastric infusion.
Conclusions  These findings support the hypothesis of the existence of a physiological oesophago-gastric feedback mechanism that might contribute to regulation of postprandial gastric acidity. Oesophageal acidification might decode gastric information and signal the stomach to decrease gastric acidity. Further studies are needed to assess the characteristics of such feedback mechanism in-patients with gastro-oesophageal reflux disease (GERD).     

Effects of a single dose of rabeprazole 20 mg and pantoprazole 40 mg on 24‐h intragastric acidity and oesophageal acid exposure: a randomized study in gastro‐oesophageal reflux disease patients with a history of nocturnal heartburn

Aliment Pharmacol Ther 31 , 991–1000

Summary

Background Nocturnal heartburn is common in patients with gastro‐oesophageal reflux disease (GERD). Aim To compare the effects of single doses of rabeprazole 20 mg and pantoprazole 40 mg on 24‐h intragastric acidity and oesophageal acid exposure (OAE). Methods A total of 52 subjects with GERD and a ≥6‐month history of heartburn were randomized into a blinded, 2 × 2 crossover trial. Subjects’ intragastric pH was monitored in two 48‐h study periods with 6‐ to 13‐day washout between periods. Patients received placebo on day 1, a single dose of rabeprazole 20 mg or pantoprazole 40 mg on day 2, and standardized meals throughout. Results The mean percentage time with intragastric pH >4 was significantly greater with rabeprazole vs. pantoprazole for the 24‐h postdose interval (44.0% vs. 32.8%; P < 0.001). Significant differences were observed in the daytime (51.0% vs. 42.2%; P < 0.001) and nighttime (32.0% vs. 16.9%; P < 0.001). Rabeprazole was also significantly superior in other intragastric pH parameters. There was no statistical difference for OAE between treatments. Conclusions In GERD patients with nocturnal heartburn, rabeprazole 20 mg was significantly more effective than pantoprazole 40 mg in percentage time with intragastric pH >4 during the nighttime, daytime, and 24‐h periods. Differences between treatments in OAE were not demonstrated. This trial is registered with http://clinicaltrials.gov , number NCT00237367.     

A single dose of ranitidine 150 mg modulates oesophageal acid sensitivity in patients with functional heartburn

BACKGROUND: The rapid onset and symptomatic response to histamine-2 receptor antagonists prior to the pharmacological effect on acid secretion suggests a different mechanism of action. AIM: To determine if ranitidine decreases oesophageal sensitivity to chemical and mechanical stimulation, potentially via oesophageal histamine receptors. METHODS: A total of 18 patients with functional heartburn received oral ranitidine 150 mg b.d. or placebo for 7 consecutive days in a double-blind randomized crossover design and underwent Barostat balloon distention and Bernstein acid infusion on study day 1 (90 min postdose) and study day 7. First sensation and pain were recorded and pain severity was rated on a 5-point Likert scale and a 100 mm visual analogue scale. Least square mean values were generated and one-tailed t-tests were performed. RESULTS: After a single dose of ranitidine 150 mg, time to pain with oesophageal acid infusion was increased by 29% (P < 0.05) and visual analogue scale and Likert scores were decreased by 20% (P < 0.06) and 23% (P < 0.02), respectively compared with placebo. After 1 week of ranitidine, positive alterations in sensory parameters persisted. Balloon distention sensory parameters were not altered by ranitidine. CONCLUSIONS: Ranitidine significantly decreased oesophageal sensitivity to acid. Failure of ranitidine to improve balloon sensory parameters supports existence of multiple sensory pathways in the oesophagus.     

The effect of formulation on oesophageal transit

The oesophageal transit of barium sulphate in small or large, heavy or light capsules or film coated and plain oval tablets was measured during fluoroscopy in five separate studies involving 175 subjects. Transit of large, but not small capsules was significantly faster than plain oval tablets in both erect and supine subjects (P less than 0.05). Heavy large capsules entered the stomach in all subjects within 20 s, whereas in all other studies some subjects retained dosage forms in the oesophagus for over 5 min. The transit of heavy capsules was significantly faster than light capsules in erect subjects (P less than 0.0005). Light capsules tended to have faster transit times than heavy capsules in the supine position. Film coating significantly enhanced oval tablet transit in erect (P less than 0.00003) and supine subjects (P less than 0.05). When large capsules of equal weight but less dense than film coated oval tablets were directly compared, the tablet transit was significantly superior in the erect subjects (P less than 0.0001). In supine subjects the transit of the light capsule was significantly faster (P less than 0.005). It is concluded that different drug formulations can have significant effects on oesophageal transit, and hence on the development of drug induced oesophageal ulceration.     

The effect of cholecystokinin antagonism on postprandial lower oesophageal sphincter function in asymptomatic volunteers and patients with reflux disease

BACKGROUND: Postprandial acid reflux is thought to be mediated by the increase in transient lower oesophageal sphincter relaxations (TLOSR) frequency and fall in lower oesophageal sphincter (LOS) pressure seen after ingestion of a meal. Studies in animals and healthy volunteers suggest that cholecystokinin (CCK) may play a role. AIM: To study the role of CCK in postprandial LOS function using the CCK antagonist loxiglumide. SUBJECTS: 10 asymptomatic volunteers (7 male, 20-29 years) and 9 patients with symptomatic gastro-oesophageal reflux (4 male, 33-66 years). METHODS: Oesophageal, LOS and gastric pressure and oesophageal pH readings were recorded for 1 h before and 2 h after intragastric infusion of a 200 kCal, 300 mL long chain triglyceride meal. Each subject underwent two studies and received intravenous loxiglumide or placebo infusion in randomized order. RESULTS: During placebo infusion, postprandial LOS pressure fell [volunteers: 17 (9-31) to 7 (1-19) mmHg (P < 0.01), patients: 15 (6-26) to 9 (2-21) mmHg (P=0.02)] and TLOSR frequency increased [volunteers: 0 (0-1) to 2 (0-7) per hour (P=0.01), patients: 0 (0-3) to 2 (0-10) per hour (P=0.03)]. Loxiglumide infusion attenuated the postprandial fall in LOS pressure and the postprandial increase in TLOSR frequency [volunteers: 0 (0-3) per hour (P=0.04 vs. placebo), patients: 0 (0-2) per hour (P=0.03 vs. placebo)], but it had only modest effects on postprandial acid exposure [volunteers: placebo 45 (0-1725) vs. loxiglumide 0 (0-443) seconds (N.S.), patients: placebo 60 (0-3442) seconds vs. loxiglumide 31 (0-1472) seconds (N.S.)]. CONCLUSIONS: Loxiglumide inhibits TLOSR and attenuates the fall in LOS pressure following a meal, but has only modest effects on postprandial gastro-oesophageal acid reflux.     

Fasting and postprandial absorption of digoxin from a microencapsulated formulation

Summary The absorption of digoxin from a capsule preparation containing a large number of small, enteric-coated granules of the glycoside (Preparation CR) was compared in 10 volunteers with that from a rapidly dissolving tablet (Preparation L). Plasma and urine digoxin concentrations were measured by radioimmunoassay. In the fasting state, after a loading dose of digoxin (0.76 mg), peak plasma concentrations were significantly (p<0.001) lower after CR (2.0±0.5 nmol/l, mean±SD) than L (4.7±1.1 nmol/l). Peak concentrations after CR were significantly (p<0.001) delayed compared to L (3.3±0.6 h vs 1.1±0.4 h). Also, postprandial peak plasma concentrations at steady state, were significantly (p<0.01) lower after CR (1.0±0.3 nmol/l) than L (2.7±0.5 nmol/l), and the peak concentrations occurred later (3.9±1.7 h vs 1.4±0.9 h). The area under the plasma concentration-time curves was smaller (p<0.01) for CR (17.7±5.9 nmol·l⁻¹·h) than for L (22.4±4.1 nmol·l⁻¹·h), and so was the amount of drug excreted in urine (174±25 μg vs 190±31 μg; p<0.005). Thus, the absorption rate of digoxin from the enteric-coated formulation was markedly reduced but at the cost of a variable reduction in the amount absorbed.     

Postprandial oesophageal integrated acidity is a reliable predictor of gastro-oesophageal reflux disease

Background : Measurement of oesophageal acid exposure parameters postprandially has been shown to distinguish gastro‐oesophageal reflux disease patients from normal individuals. Aims : To calculate the accuracy of postprandial oesophageal integrated acidity in diagnosing gastro‐oesophageal reflux disease. Methods : Ambulatory 24‐h pH studies of 626 patients were analysed retrospectively. Gastro‐oesophageal reflux disease, defined as pH < 4 for >4.2% of time, was identified in 305 subjects. Postprandial oesophageal integrated acidity was measured for 2 and 3 h after the largest meal peak as determined from gastric pH. Postprandial symptom‐associated probability was calculated. Results : Gastro‐oesophageal reflux disease subjects had a greater postprandial oesophageal integrated acidity than non‐gastro‐oesophageal reflux disease subjects [median (IQR): 0.57 (0.08–2.66) vs. 0.03 (0.01–0.15) mmol*h/L]. Median postprandial oesophageal integrated acidity did not differ with gender or age in gastro‐oesophageal reflux disease and non‐gastro‐oesophageal reflux disease subjects (P > 0.05 for all). A 3‐h postprandial oesophageal integrated acidity value of 0.121 mmol*h/L had a 71.1% sensitivity and 71.7% specificity in diagnosing gastro‐oesophageal reflux disease. Gastro‐oesophageal reflux disease subjects with symptoms had a higher postprandial oesophageal integrated acidity than those without (P = 0.043), whereas non‐gastro‐oesophageal reflux disease subjects with and without symptoms did not differ (P = 0.74). The correlation between symptom‐associated probability and postprandial oesophageal integrated acidity was poor (gastro‐oesophageal reflux disease: r = 0.15; non‐gastro‐oesophageal reflux disease: r = 0.25). Conclusion : Postprandial oesophageal integrated acidity provides a robust estimation of oesophageal acid exposure and may predict symptoms in gastro‐oesophageal reflux disease patients.     

Determination of the reduction in gastric acidity necessary to prevent pathological oesophageal reflux in patients with gastro-oesophageal reflux disease treated with a proton pump inhibitor

BACKGROUND: In subjects with gastro-oesophageal reflux disease treated with a gastric antisecretory agent, the extent to which gastric acidity needs to be reduced to prevent pathological oesophageal acid exposure is not known. METHODS: Gastric and oesophageal pH were measured in 26 healthy subjects and in 59 subjects with gastro-oesophageal reflux disease. In 27 of the subjects with gastro-oesophageal reflux disease, pH was also recorded on days 1, 2 and 8 of treatment with 20 mg omeprazole and 20 mg rabeprazole in a randomized, two-way, cross-over fashion. RESULTS: Receiver operating characteristic analysis was used to determine values for the integrated oesophageal acidity and time oesophageal pH相似文献   

肠内免疫营养对食管癌病人免疫反应及蛋白质代谢作用的影响

目的:研究肠内免疫营养对食管癌手术后病人免疫功能及蛋白质代谢的影响.方法:将42例食管癌病人随机分为肠内免疫营养组(研究组)和常规肠内营养组(对照组),分别于术后第2～8天给予等氮、等热量的肠内营养支持.于手术前1天、术后第1天和第9天分别检测IgG、IgM、IgA、总淋巴细胞数,用药期间留24h尿计量,用自动生化仪检测24h尿中尿素和肌苷排泄量.结果:研究组IgA、总淋巴细胞数均显著高于对照组,24h尿尿素和肌苷排泄量显著低于对照组.结论:肠内免疫营养可提高食管癌术后病人免疫力,改善机体蛋白质代谢功能.     

Predictors of heartburn resolution and erosive esophagitis in patients with GERD

ABSTRACT

Objectives: The primary objective was to assess gastroesophageal reflux disease (GERD) symptom resolution rates with esomeprazole by erosive esophagitis (EE) status, and the secondary objective was to evaluate potential predictors of the presence of EE and heartburn resolution.

Background: Patients with GERD who have EE have higher reported symptom resolution rates than those with nonerosive reflux disease (NERD) when treated with proton pump inhibitors (PPIs).

Study: This open-label multicenter study included adults with GERD symptoms. Patients were stratified by EE status after endoscopy and received once-daily esomeprazole 40?mg for 4 weeks. Questionnaires determined symptom response rates, and baseline predictors of EE or heartburn resolution were evaluated. Potential predictors, including years with GERD, history of EE, and time to relief with antacids, were examined.

Results: Heartburn resolution rates at 4 weeks were higher for patients with EE than NERD (69% [124/179] vs. 48% [85/177]; p?<?0.0001). Multivariate models had moderate predictive ability for EE (c-index, 0.76) and poor predictive ability (c-index, 0.57) for heartburn resolution. However, faster heartburn relief with antacid use, particularly within 15?min, was predictive of EE and heartburn resolution.

Conclusions: Patients with EE have higher heartburn resolution rates than patients with NERD after treatment, although recall bias may be possible. Fast relief with antacid use is predictive of EE and heartburn resolution with a PPI and suggests that a history of antacid relief may provide corroborative evidence to empiric PPI therapy in determining whether patients with heartburn have acid reflux disease.

Trial registration: ClinicalTrials.gov identifier: NCT00242736.     

Effects of arotinolol on regional cerebral blood flow in hypertensive patients with a history of stroke

Although optimal blood pressure control is important for managing stroke patients, the use of antihypertensives in stroke patients often causes cerebral blood flow reduction leading sometimes to deterioration of symptoms. Effects of arotinolol, a β-blocker with a moderate α-blocking action, on the regional cerebral blood flow (rCBF) were investigated in 10 hypertensive patients with a history of stroke by using a noninvasive ¹³³Xe inhalation method. The rCBF was measured before and after administration of 15 mg/day arotinolol (three times a day) for 2–3 weeks. After the administration, the blood pressure was reduced in all the patients showing a change in average values of from 176/105 mmHg to 152/90 mmHg. The rCBF in the infarcted and healthy hemispheres was 44.3 ± 4.4 and 44.6 ± 5.0 ml/100 g/min before arotinolol and 44.9 ± 6.4 and 45.3 ± 6.5 ml/100 g/min after arotinolol, respectively. No significant rCBF change was observed after arotinolol in both hemispheres. During the administration, none of the patients suffered from dizziness or other ischemic symptoms. The above results suggest that arotinolol exerts little influence on the cerebral circulation and may be useful for the management of hypertension in stroke patients.     

Effects of nutrients on postprandial lipemia

Numerous factors including diet, lifestyle conditions, genetic background and physio-pathological conditions modulate the amplitude and time-courses of postprandial changes in humans. This review focuses on dietary factors affecting postprandial lipemia and lipoproteins metabolism in humans. The known effects of amount or type of fat, carbohydrate, protein and fiber are summarized. Changing the habitual dietary pattern can also alter the postprandial response. This review highlights that postprandial metabolism is a key link between dietary pattern and cardiovascular health or risk.     

Effects of a fast disintegrating/rapid release oral formulation of sumatriptan on functional ability in patients with migraine

BACKGROUND: A new oral form of sumatriptan has been developed to facilitate tablet disintegration and drug dispersion and to mitigate the effects of gastric stasis that can accompany migraine. OBJECTIVE: To evaluate the effects on functional ability of the new fast disintegrating/rapid release formulation of sumatriptan. METHODS: Sumatriptan 50 mg (n = 137), 100 mg (n = 142), or placebo (n = 153) was administered early when pain was mild for the acute treatment of a single migraine attack in a randomized, double-blind, parallel-group, placebo-controlled clinical trial. For this report, main health-outcomes endpoints (which were secondary endpoints for this clinical trial that was primarily designed to assess pain-free efficacy) included functional ability measured through 2 h postdose on a 5-point scale and lost time equivalents, a composite measure of migraine-associated time missed from activities, and reduced effectiveness at activities through 24 h postdose. RESULTS: Normal functional ability was restored in a significantly (p < 0.05) greater percentage of patients treated with sumatriptan than placebo beginning 45 min postdose for sumatriptan 100 mg and 1 h postdose for sumatriptan 50 mg. During the 24 h after initial dosing, the median (range) lost time equivalents for the combination of paid work activities and activities outside of paid work were significantly lower in the groups treated with sumatriptan (1.1 [0-10] sumatriptan 100 mg; 0.8 [0-36] sumatriptan 50 mg) compared with placebo (2.9 [0-24]) (p < or = 0.01 each sumatriptan group versus placebo). The corresponding mean +/- SD values for lost time equivalents were 1.9 +/- 2.3 and 2.5 +/- 4.7 for sumatriptan 100 mg and 50 mg, respectively, compared with 3.5 +/- 4.3 for placebo. CONCLUSION: A new oral sumatriptan formulation confers rapid, sustained restoration of functional ability in the acute treatment of migraine so that patients can return rapidly to normal functioning at work and outside of work.